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The unique acute effects of the large fractional doses that characterize stereotactic radiosurgery (SRS) or radiotherapy (SRT), specifically in terms of antitumor immune cellular processes, vascular damage, tumor necrosis, and apoptosis on brain metastasis have yet to be empirically demonstrated. The objective of this study is to provide the first in-human evaluation of the acute biological effects of SRS/SRT in resected brain metastasis. Tumor samples from patients who underwent dose-escalated preoperative SRT followed by resection with available non-irradiated primary tumor tissues were retrieved from our institutional biorepository. All primary tumors and irradiated metastases were evaluated for the following parameters: tumor necrosis, T-cells, natural killer cells, vessel density, vascular endothelial growth factor, and apoptotic factors. Twenty-two patients with irradiated and resected brain metastases and paired non-irradiated primary tumor samples met inclusion criteria. Patients underwent a median preoperative SRT dose of 18 Gy (Range: 15-20 Gy) in 1 fraction, with 3 patients receiving 27-30 Gy in 3-5 fractions, followed by resection within median interval of 67.8 h (R: 18.25-160.61 h). The rate of necrosis was significantly higher in irradiated brain metastases than non-irradiated primary tumors (p < 0.001). Decreases in all immunomodulatory cell populations were found in irradiated metastases compared to primary tumors: CD3 + (p = 0.003), CD4 + (p = 0.01), and CD8 + (p = 0.01). Pre-operative SRT is associated with acute effects such as increased tumor necrosis and differences in expression of immunomodulatory factors, an effect that does not appear to be time dependent, within the limited intervals explored within the context of this analysis.

The unique acute effects of the large fractional doses that characterize stereotactic radiosurgery (SRS) or radiotherapy (SRT), specifically in terms of antitumor immune cellular processes, vascular damage, tumor necrosis, and apoptosis on brain metastasis have yet to be empirically demonstrated. The objective of this study is to provide the first in-human evaluation of the acute biological effects of SRS/SRT in resected brain metastasis. Tumor samples from patients who underwent dose-escalated preoperative SRT followed by resection with available non-irradiated primary tumor tissues were retrieved from our institutional biorepository. All primary tumors and irradiated metastases were evaluated for the following parameters: tumor necrosis, T-cells, natural killer cells, vessel density, vascular endothelial growth factor, and apoptotic factors. Twenty-two patients with irradiated and resected brain metastases and paired non-irradiated primary tumor samples met inclusion criteria. Patients underwent a median preoperative SRT dose of 18 Gy (Range: 15-20 Gy) in 1 fraction, with 3 patients receiving 27-30 Gy in 3-5 fractions, followed by resection within median interval of 67.8 h (R: 18.25-160.61 h). The rate of necrosis was significantly higher in irradiated brain metastases than non-irradiated primary tumors (p < 0.001). Decreases in all immunomodulatory cell populations were found in irradiated metastases compared to primary tumors: CD3 + (p = 0.003), CD4 + (p = 0.01), and CD8 + (p = 0.01). Pre-operative SRT is associated with acute effects such as increased tumor necrosis and differences in expression of immunomodulatory factors, an effect that does not appear to be time dependent, within the limited intervals explored within the context of this analysis.

BackgroundThe objective of this study was to evaluate the impact of the time interval between planning imaging and stereotactic radiosurgery (SRS) delivery on tumor volumes and spatial anatomic displacements of brain metastases (BM).MethodsConsecutive patients diagnosed with BM treated with SRS over a 3-year period were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) were included. The impact of histology, inter-scan time interval, lesion location, tumor volume, and diameter were evaluated on final lesion diameter, volume, anatomic displacement, and ultimate need for change in management (ie, expanding margins, rescanning).Results101 patients (531 lesions) with a median inter-scan time interval of 8 days (range: 1-42 days) met the inclusion criteria. The median percentage increase in BM diameter and volume were 9.5% (IQR: 2.25%-24.0%) and 20% (IQR: 0.7%-66.7%). Overall, 147 lesions (27.7%) in 57 patients (56.4%) required a change in management. There was a statistically significant relationship between initial tumor diameter (cm) and change in management (OR: 2.69, 95% CI: 1.93-3.75; P < .001). Each day between MRI-1 and MRI-2 was associated with a change in management with an OR of 1.05 (95% CI: 1.03-1.07; P < .001).ConclusionsChanges in tumor diameter, volume, and spatial position occur as a function of time. Planning imaging for SRS is recommended to occur in close temporal proximity to treatment; for those with delays, a larger setup margin may need to be used to ensure tumor coverage and account for positional changes.

A series of oriented electrospun nylon fibers were prepared with nominal fiber diameters of either 300 nm or 1 m. In addition, a series of similar mats were prepared that contained a hyperbranched polymer additive to act as a surface modifier for the fibers. The mats were used as reinforcements for epoxy composites. The composite coupons were interrogated using techniques such as dynamic mechanical analysis and tensile testing. While the nanofibers did not dramatically stiffen the resulting composites, they provided insight as to the impact of the additives on the interaction of the fibers with the composite matrix. The inclusion of the additive appeared to improve interfacial interactions of the fibers with the matrix, as reduced void content and uniform fracture interfaces were observed in the modified composites. While the low production rate of suitable fiber mats for this study limited the scope and accessibility of test specimens, the results from the examination of fiber-matrix interfaces argues for further investigation., The original document contains color images. Prepared in collaboration with Oak Ridge Institute for Science and Education, Belcamp, MD and Bowhead Science and Technology, Alexandria, VA.

BackgroundThere is notable heterogeneity in the clinical presentation of patients with COPD. To characterise this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene study.MethodsWe applied a clustering method, k-means, to data from 10 192 smokers in the COPDGene study. After splitting the sample into a training and validation set, we evaluated three sets of input features across a range of k (user-specified number of clusters). Stable solutions were tested for association with four COPD-related measures and five genetic variants previously associated with COPD at genome-wide significance. The results were confirmed in the validation set.FindingsWe identified four clusters that can be characterised as (1) relatively resistant smokers (ie, no/mild obstruction and minimal emphysema despite heavy smoking), (2) mild upper zone emphysema-predominant, (3) airway disease-predominant and (4) severe emphysema. All clusters are strongly associated with COPD-related clinical characteristics, including exacerbations and dyspnoea (p<0.001). We found strong genetic associations between the mild upper zone emphysema group and rs1980057 near HHIP, and between the severe emphysema group and rs8034191 in the chromosome 15q region (p<0.001). All significant associations were replicated at p<0.05 in the validation sample (12/12 associations with clinical measures and 2/2 genetic associations).InterpretationCluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants.

BackgroundCOPD patients have a great burden of comorbidity. However, it is not well established whether this is due to shared risk factors such as smoking, if they impact patients exercise capacity and quality of life, or whether there are racial disparities in their impact on COPD.MethodsWe analyzed data from 10,192 current and ex-smokers with (cases) and without COPD (controls) from the COPDGene® cohort to establish risk for COPD comorbidities adjusted for pertinent covariates. In adjusted models, we examined comorbidities prevalence and impact in African-Americans (AA) and Non-Hispanic Whites (NHW).ResultsComorbidities are more common in COPD compared to those with normal spirometry (controls), and the risk persists after adjustments for covariates including pack-years smoked. After adjustment for confounders, eight conditions were independently associated with worse exercise capacity, quality of life and dyspnea. There were racial disparities in the impact of comorbidities on exercise capacity, dyspnea and quality of life, presence of osteoarthritis and gastroesophageal reflux disease having a greater negative impact on all three outcomes in AAs than NHWs (p<0.05 for all interaction terms).ConclusionsIndividuals with COPD have a higher risk for comorbidities than controls, an important finding shown for the first time comprehensively after accounting for confounders. Individual comorbidities are associated with worse exercise capacity, quality of life, and dyspnea, in African-Americans compared to non-Hispanic Whites.

Antimicrobial coatings deposited onto ultra high molecular weight polyethylene (UHMWPE) films were investigated using an atmospheric pressure plasma enhanced chemical vapor deposition (AP-PECVD) process. Varying concentrations of a guanidine-based liquid precursor, 1,1,3,3-tetramethylguanidine, were used, and different deposition conditions were studied. Attenuated total reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy and X-ray Photoelectron Spectroscopy (XPS) were used to study the chemical structure and elemental composition of the coatings. Conformity, morphology, and coating thickness were assessed through SEM and AFM. Optimal AP-PECVD parameters were chosen and applied to deposit guanidine coatings onto woven fabrics. The coatings exhibited high antimicrobial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) based on a modified-AATCC 100 test standard, where 2 5 log reductions were achieved., The original document contains color images. Published in ACS Applied Materials & Interfaces, v5 p11836-11843, 29 Oct 2013.

The self-decontaminating coatings project is a collaborative effort between the U.S. Air Force Research Laboratory (AFRL), the U.S. Army Research Laboratory (ARL), the Naval Research Laboratory (NRL), and the Edgewood Chemical and Biological Center. The program focuses on the research and development of coatings with self-decontaminating or self-cleaning properties toward chemical warfare agents, such as O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) or bis(2-chloroethyl) sulfide (HD)., Prepared in collaboration with Oak Ridge Institute for Science and Education, Oak Ridge, TN. The original document contains color images.

Fluorescent dyes were studied in an effort to develop molecules suitable to signal the onset of metal corrosion under a paint or coating. Rhodamine B and fluorescein were chemically modified to determine the effect of steric hindrance and electron withdrawing/donating substituents on the selective binding of these dyes to various metals. Rhodamine B and fluorescein were converted into the corresponding hydrazide to provide a precursor material. The hydrazides were then reacted with various diphenyl and dialkyl ketones to determine the impact of bulky groups on dye-metal binding. Electronic effects were probed as the hydrazide precursors were reacted with various aldehydes that contained substituted phenyl rings. Fluorescence measurements were used to determine the impact of each substitution on dye-metal binding efficiency and selectivity., The original document contains color images.

Fluorescent dyes were studied in an effort to develop molecules suitable to signal the onset of metal corrosion under a paint or coating. Rhodamine B and fluorescein were chemically modified to determine the effect of steric hindrance and electron withdrawing/donating substituents on the selective binding of these dyes to various metals. Rhodamine B and fluorescein were converted into the corresponding hydrazide to provide a precursor material. The hydrazides were then reacted with various diphenyl and dialkyl ketones to determine the impact of bulky groups on dye-metal binding. Electronic effects were probed as the hydrazide precursors were reacted with various aldehydes that contained substituted phenyl rings. Fluorescence measurements were used to determine the impact of each substitution on dye-metal binding efficiency and selectivity., The original document contains color images.

The continued deployment of military assets overseas will introduce military personnel, vehicles, and other assets to microscopic pathogenic species. Bacterial infections can complicate treatment and lengthen recovery time. Development of self-decontaminating surfaces would lessen bacterial contamination by preventing bacterial growth on military vehicles and other surfaces. This project has developed spontaneously segregating multifunctional additives capable of insertion into current military coatings to reduce susceptibility to bacterial contamination of military assets., The original document contains color images.

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